Research Focus

The entire nature of tumor cells and their communication with the microenvironment is complex. We are interested in the mechanism, which drive the dissemination of tumor cells from the primary tumor and allow the survival of these cells in the circulation and finally their evasion. An import role in these processes plays the bone morphogenetic protein signaling network. In collaboration with partners from academia and industry we develop new procedures to identify and isolate the entirety of circulating tumor cells from the peripheral blood. Novel photonic technologies and innovative nanomaterials contribute to a significant part to this approach.

Innovative nanomaterials in hematology and oncology

Magnetic metallic nanoparticles are widely used tools to isolate and label cells, e.g. circulating tumor cells. We are interested in understanding the cellular processes during the interaction of nanomaterials with human cells. In focus are overall cell vitality, intracellular transport mechanisms and inflammatory response. The life cycle of nanomaterials is studied in long-term cell culture models.

Identification and characterization of circulating tumor cells

The detection and identification of circulating tumor cells is challenging. The proportion of these cells is very low in the peripheral blood of tumor patients. The cell population is highly variable which requires an in-depth investigation on a single cell level. A further characterization on the molecular level is needed for future advances in cancer diagnosis and therapy.

Tumor biology of Bone Morphogenetic Proteins

Bone morphogenetic proteins are a subgroup of the Transforming Growth Factor beta superfamily. They are important regulators of embryogenesis, organogenesis and tumorigenesis. We could show that BMP-2 keeps cells in a “susceptible state” that can take various directions depending on further signals.

Publications (Selection)

2021

2021

Daum, A.K., Dittmann, J., Jansen, L., Peters, S., Dahmen, U., Heger, J., Hoppe-Seyler, F., Gille.A., Clement, J.H., Runnebaum, I.B., Dürst, M., Backsch, C. 2021. ITIH5 shows tumor suppressive properties in cervical cancer cells grown as multicellular tumor spheroids. American Journal of Translational Research 13: 10298-10314. eCollection 2021

Mickoleit, F., Jörke, C., Geimer, S., Maier, D., Müller, J.P., Demut, J., Gräfe, C., Schüler, D., Clement, J.H. 2021. Biocompatibility, uptake and subcellular localization of bacterial magnetosomes in mammalian cells. Nanoscale Advances 3: 3799-3815; https://doi.org/10.1039/D0NA01086C

Gericke, M., Geitel, K., Jörke, C., Clement, J.H., Heinze, T. 2021. Reactive nanoparticles derived from polysaccharide phenyl carbonates. Molecules 26: 4026; https://doi.org/10.3390/molecules26134026

Gräfe, C., Müller, E., Gresing, L., Weidner, A., Radon, P., Friedrich, R., Alexiou, C., Wiekhorst, F., Dutz, S., Clement, J.H. 2021. Magnetic hybrid materials interact with biological matrices – Interaction of magnetic nanoparticles with cellular barriers. Physical Sciences Reviews: https://doi.org/10.1515/psr-2019-0114

Dutz, S., Weidner, A., von der Lühe, M., Gräfe, C., Biehl, P., Demut, J., Warncke, P., Jungmann, S., Fischer, D., Schacher, F.H., Clement, J.H. 2021. Hybrid Nanomaterials of Biomolecule Corona Coated Magnetic Nanoparticles and Their Interaction with Biological Systems. Physical Sciences Reviews: https://doi.org/10.1515/psr-2019-0110

Gresing, L.J., Radon, P., Friedrich, R.P., Zahn, D., Raasch, M., Mosig, A.S., Dutz, S., Alexiou, C., Wiekhorst, F., Hochhaus, A., Clement, J.H. 2021. Negatively charged magnetic nanoparticles pass the blood-placenta barrier under continuous flow conditions in a time-dependent manner. Journal of Magnetism and Magnetic Materials 521: 167535; doi.org/10.1016/j.jmmm.2020.167535

Rosenfeldt, S., Mickoleit, F., Jörke, C., Clement, J.H., Markert, S., Jérôme, V., Schwarzinger, S., Freitag, R., Schüler, D., Uebe, R., Schenk, A.S. 2021. Towards standardized purification and regeneration of bacterial magnetic nanoparticles for future in vivo applications. Acta Biomaterialia 120: 293-303

2020

Ernst, P., Press, A.T., Fischer, M., Schäfer, V., Gräfe, C., Clement, J.H., Ernst, T., Schubert, U.S., Bauer, M., Hochhaus, A. 2020. Polymethine dye-functionalized nanoparticles as a specific drug delivery system for the eradication of CML stem cells. Molecular Therapy – Oncolytics 18: 372-381

Dutz, S., Buske, N., Landers, J., Gräfe, C., Wende, H., Clement, J.H. 2020. Biocompatible magnetic fluids of Co-doped iron oxide nanoparticles with tunable magnetic properties. Nanomaterials: 10: 1019; doi.org/10.3390/nano10061019

2019

Mihajlović, J., Diehl, L.M.A., Hochhaus, A., Clement J.H. 2019. Inhibition of bone morphogenetic protein signaling reduces viability, growth and migratory potential of non-small cell lung carcinoma cells. J. Cancer Res. Clin. Oncol. 145: 2675-2687.

Alcala, N., Leblay, N., Gabriel, A., Mangiante, L., Hervas Marin, D., Giffon, T., Sertier, A.S., Ferrari, a., Derks, J., Ghantous, A., Delhomme, T.M., Chabrier, A., Cuenin, C., Abedi-Ardekani, B., Boland, A., Caux, C., Altmueller, A., Durand, G., Voegele, C., Boyault, S., Lemaitre, N., Lorimier, P., Toffart, A.C., Mc Leer, A., Solterman, A., Clement, J.H., Saenger, J., Field, J.K., Brevet, M., Blanc-Fournier, C., Galateau-Salle, F., Le Stang, N., Damiola, F., Russell, P., Wright, G., Roz, L., Lacomme, S., Vignaug, J.M., Hofman, V., Hofman, P., Brustugun, O.T., Lund-Iversen, M., Thomas de Montpreville, V., Muscarella, L.A., Graziano, P., Volante, M., Papotti, M.G., Brcic, L., Popper, H., Deleuze, J.F., Herceg, Z., Viari, A., Nuernberg, P., McKay, J.D., Sandoval, J., Hernandez-Vargas, H., Brambilla, E., Speel, E.J., Girard, N., Lantuejoul, S., Foll, M., Fernandez-Cuesta, L. 2019. Integrative and comparative analyses of multi-omics data identify clinically relevant molecular groups of pulmonary carcinoids and unveil the existence of supra-atypical carcinoids. Nature Commun. 10: 3407; doi.org/10.1038/s41467-019-11276-9

Gräfe, C., von der Lühe, M., Weidner, A., Globig, P., Clement, J.H., Dutz, S., Schacher, F.H. 2019. Protein Corona Formation and its Constitutional Changes on Magnetic Nanoparticles in Serum featuring a Polydehydroalanine Coating: Effects of Charge and Incubation Conditions. Nanotechnology 30(26):265707. doi: 10.1088/1361-6528/ab0ed0

2018

Müller, E.K., Gräfe, C., Wiekhorst, F., Bergemann, C., Weidner, A., Dutz, S., Clement, J.H. 2018. Magnetic nanoparticles interact and pass an in vitro co-culture blood-placenta model. Nanomaterials 8: 108; doi:10.3390/nano8020108

George, J., Walter, V., Peifer, M., Alexandrov, L.B., Seidel, D., Leenders, F., Maas, L., Müller, C., Dahmen, I., Delhomme, T.M., Ardin, M., Leblay, N., Byrnes, G., Sun, R., De Reynies, A., McLeer-Florin, A., Bosco, G., Malchers, F., Menon, R., Altmüller, J., Becker, C., Nürnberg, P., Achter, V., Lang, U., Schneider, P.M., Bogus, M., Soloway, M.G., Wilkerson, M.D., Cun, Y., McKay, J.D., Moro-Sibilot, D., Brambilla, C.G., Lantuejoul, S., Lemaitre, N., Soltermann, A., Weder, W., Tischler, V., Brustugun, O.T., Lund-Iversen, M., Helland, Å., Solberg, S., Ansén, S., Wright, G., Solomon, B., Roz, L., Pastorino, U., Petersen, I., Clement, J.H., Sänger, J., Wolf, J., Vingron, M., Zander, T., Perner, S., Travis, W.D., Haas, S.A., Olivier, M., Foll, M., Büttner, R., Hayes, D.N., Brambilla, E., Fernandez-Cuesta, L., Thomas, R.K. 2018. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nat Commun. 9: 1048.

Complete list of publications here.

Funding

Deutsche Forschungsgemeinschaft
BMBF
Dr. Rainald Stromeyer-Stiftung